1. Field of the Invention
This invention relates generally to medical device systems and, more particularly, to medical device systems for applying electrical signals to a cranial nerve for the treatment of medical conditions, and for improved electrical signals in such systems.
2. Description of the Related Art
Many advancements have been made in treating diseases such as depression and epilepsy. Therapies using electrical signals for treating these diseases have been found to be effective. Implantable medical devices have been effectively used to deliver therapeutic stimulation to various portions of the human body (e.g., the vagus nerve) for treating these diseases. As used herein, “stimulation” or “stimulation signal” refers to the application of an electrical, mechanical, magnetic, electromagnetic, photonic, audio and/or chemical signal to a neural structure in the patient's body. The signal is an exogenous signal that is distinct from the endogenous electrical, mechanical, and chemical activity (e.g., afferent and/or efferent electrical action potentials) generated by the patient's body and environment. In other words, the stimulation signal (whether electrical, mechanical, magnetic, electro-magnetic, photonic, audio or chemical in nature) applied to the nerve in the present invention is a signal applied from an artificial source, e.g., a neurostimulator.
A “therapeutic signal” refers to a stimulation signal delivered to a patient's body with the intent of treating a medical condition by providing a modulating effect to neural tissue. The effect of a stimulation signal on neuronal activity is termed “modulation”; however, for simplicity, the terms “stimulating” and “modulating”, and variants thereof, are sometimes used interchangeably herein. In general, however, the delivery of an exogenous signal itself refers to “stimulation” of the neural structure, while the effects of that signal, if any, on the electrical activity of the neural structure are properly referred to as “modulation.” The modulating effect of the stimulation signal upon the neural tissue may be excitatory or inhibitory, and may potentiate acute and/or long-term changes in neuronal activity. For example, the “modulating” effect of the stimulation signal to the neural tissue may comprise one more of the following effects: (a) initiation of an action potential (afferent and/or efferent action potentials); (b) inhibition or blocking of the conduction of action potentials, whether endogenous or exogenously induced, including hyperpolarizing and/or collision blocking, (c) affecting changes in neurotransmitter/neuromodulator release or uptake, and (d) changes in neuro-plasticity or neurogenesis of brain tissue.
In some embodiments, electrical neurostimulation may be provided by implanting an electrical device underneath the skin of a patient and delivering an electrical signal to a nerve such as a cranial nerve. In one embodiment, the electrical neurostimulation involves sensing or detecting a body parameter, with the electrical signal being delivered in response to the sensed body parameter. This type of stimulation is generally referred to as “active,” “feedback,” or “triggered” stimulation. In another embodiment, the system may operate without sensing or detecting a body parameter once the patient has been diagnosed with a medical condition that may be treated by neurostimulation. In this case, the system may apply a series of electrical pulses to the nerve (e.g., a cranial nerve such as a vagus nerve) periodically, intermittently, or continuously throughout the day, or over another predetermined time interval. This type of stimulation is generally referred to as “passive,” “non-feedback,” or “prophylactic,” stimulation. The electrical signal may be applied by an IMD that is implanted within the patient's body. In other cases, the signal may be generated by an external pulse generator outside the patient's body, coupled by an RF or wireless link to an implanted electrode.
Generally, neurostimulation signals that perform neuromodulation are delivered by the IMD via one or more leads. The leads generally terminate at their distal ends in one or more electrodes, and the electrodes, in turn, are electrically coupled to tissue in the patient's body. For example, a number of electrodes may be attached to various points of a nerve or other tissue inside a human body for delivery of a neurostimulation signal.
While feedback stimulation schemes have been proposed, conventional vagus nerve stimulation (VNS) usually involves non-feedback stimulation characterized by a number of parameters. Specifically, convention vagus nerve stimulation usually involves a series of electrical pulses in bursts defined by an “on-time” and an “off-time.” During the on-time, electrical pulses of a defined electrical current (e.g., 0.5-2.0 milliamps) and pulse width (e.g., 0.25-1.0 milliseconds) are delivered at a defined frequency (e.g., 20-30 Hz) for the on-time duration, usually a specific number of seconds, e.g., 10-100 seconds. The pulse bursts are separated from one another by the off-time, (e.g., 30 seconds-5 minutes) in which no electrical signal is applied to the nerve. The on-time and off-time parameters together define a duty cycle, which is the ratio of the on-time to the combination of the on-time and off-time, and which describes the percentage of time that the electrical signal is applied to the nerve.
In conventional VNS, the on-time and off-time may be programmed to define an intermittent pattern in which a repeating series of electrical pulse bursts are generated and applied to the vagus nerve. Each sequence of pulses during an on-time may be referred to as a “pulse burst.” The burst is followed by the off-time period in which no signals are applied to the nerve. The off-time is provided to allow the nerve to recover from the stimulation of the pulse burst, and to conserve power. If the off-time is set at zero, the electrical signal in conventional VNS may provide continuous stimulation to the vagus nerve. Alternatively, the idle time may be as long as one day or more, in which case the pulse bursts are provided only once per day or at even longer intervals. Typically, however, the ratio of “off-time” to “on-time” may range from about 0.5 to about 10.
In addition to the on-time and off-time, the other parameters defining the electrical signal in conventional VNS may be programmed over a range of values. The pulse width for the pulses in a pulse burst of conventional VNS may be set to a value not greater than about 1 msec, such as about 250-500 μsec, and the number of pulses in a pulse burst is typically set by programming a frequency in a range of about 20-150 Hz (i.e., 20 pulses per second to 150 pulses per second). A non-uniform frequency may also be used. Frequency may be altered during a pulse burst by either a frequency sweep from a low frequency to a high frequency, or vice versa. Alternatively, the timing between adjacent individual signals within a burst may be randomly changed such that two adjacent signals may be generated at any frequency within a range of frequencies.
Various feedback stimulation schemes have been proposed. In U.S. Pat. No. 5,928,272, the automatic activation of a neurostimulator such as a vagus nerve stimulator is described based on a detected increase in heart rate. The '272 patent notes that epilepsy attacks are sometimes preceded by increases in heart rate and proposes automatically applying an electrical signal to a vagus nerve if the patient's heart rate exceeds a certain level. The patent does not disclose initiating or synchronizing the therapeutic electrical signal with the patient's heart rhythms. Instead, detection of an abnormal heart rate is used to trigger otherwise conventional VNS.
A new type of stimulation has been proposed known as “microburst” stimulation, which provides enhanced evoked potentials in the brain (as more fully described in co-pending application Ser. No. 11/693,451, “Microburst Electrical Stimulation Of Cranial Nerves For The Treatment Of Medical Conditions”). “Enhanced” in this context refers to electrical potentials evoked in the forebrain by neurostimulation that are higher than those produced by conventional neurostimulation. The electrical signal for this improved therapy is substantially different from the electrical signals in conventional VNS. In particular, electrical signals in microburst stimulation are characterized by very short bursts of a limited number of electrical pulses. These shorts bursts of less than 1 second are referred to hereinafter as “microbursts.” By applying an electrical signal comprising a series of microbursts to, for example, a vagus nerve of a patient, enhanced vagal evoked potentials (eVEP) are produced in therapeutically significant areas of the brain. Significantly, eVEP are not produced by conventional vagus nerve stimulation.
As used herein, the term “microburst” refers to a portion of a therapeutic electrical signal comprising a limited plurality of pulses and a limited burst duration. More particularly, a microburst may comprise at least two but no more than 25 electrical pulses, and may last for no more than 1 second, and typically less than 100 milliseconds, more typically 10-80 msec. A therapeutic electrical signal may comprise a series of microbursts separated from one another by time intervals known as “interburst periods” which allow a refractory interval for the nervous system to recover from the microburst and again become receptive to eVEP stimulation by another microburst. In some embodiments, the interburst period may be as long as or longer than the adjacent microbursts separated by the interburst period. In some embodiments the interburst period may comprise an absolute time period of at least 100 milliseconds and in some embodiments, up to 6 seconds. Adjacent pulses in a microburst are separated by a time interval known as an “interpulse interval,” which may comprise a time period from 1 msec to 50 msec. The interpulse interval, together with the number of pulses and the pulse width of each pulse, determines a “microburst duration,” which is the length of a microburst from the beginning of the first pulse to the end of the last pulse (and thus the beginning of a new interburst period). Microburst duration in microburst stimulation can be 1 second or less (i.e., microbursts can be no greater than 1 second), and more preferably is 100 msec or less, and still more preferably is in the range of 10-80 msec. The pulses in a microburst may be further characterized by a current amplitude and a pulse width. Microburst stimulation may optionally include an on-time and an off-time in which the microbursts are provided and not provided, respectively, to a cranial nerve. At least one of the interburst period, the number of pulses per burst, the interpulse interval, the microburst duration, the current amplitude, the pulse width, the on-time, or the off-time are selected to enhance cranial nerve evoked potentials.
The timing of neurostimulation signals has heretofore generally conformed to standard clock cycles, without regard to the efficacy of neurostimulation signals delivered at particular time-points. The present inventor is unaware of previous investigations of the efficacy of neurostimulation signals delivered at particular time-points of physiological cycles.